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Review
. 2017 May;9(5):701-710.
doi: 10.2217/epi-2016-0097. Epub 2017 May 4.

Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence

Elizabeth M Martin  1 , Miroslav Stýblo  2   3 , Rebecca C Fry  1   3
Affiliations
Review

Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence

Elizabeth M Martin et al. Epigenomics. 2017 May.

Abstract

Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.

Keywords: arsenic; diabetes; epigenome; genome.

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Conflict of interest statement

Financial & competing interests disclosure

This work was funded by the National Institute of Health (R01ES015326, 3R01ES015326-03S1, P30ES010126, P42ES005948, R01ES019315 and T32ES007018). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Arsenic (iAsIII) and its metabolites inhibit insulin-dependent glucose uptake by disrupting the insulin-activated signaling cascade.
Specifically, iAsIII and MAsIII have been shown to inhibit the phosphorylation of Akt by PDK, resulting in inhibition of GLUT4 translocation to plasma membrane; DMAsIII inhibits signaling downstream of PDK/Akt, but the exact target has not been identified. Figure adapted from [23].
See this image and copyright information in PMC

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